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The contribution of diabetes to breast cancer remains uncertain among Chinese females, which may result from different genetic factors. We evaluated the associations of diabetes, combined with the polymorphisms in the genes of fat mass and obesity-associated gene (FTO), interleukin 6 (IL-6), and heat shock protein 60 (HSPD1), with breast cancer risk and survival in a Chinese Han population. The information on the history of diabetes was collected from 1551 incident breast cancer cases and 1605 age-frequency matched controls in Guangzhou, China. In total, 1168 cases were followed up. Diabetes was associated with both an increased risk of breast cancer [OR (95%CI): 1.67 (1.11, 2.52)] and a poor overall survival and progression free survival for breast cancer patients [HRs (95%CIs): 2.66 (1.10, 6.44) and 2.46 (1.29, 4.70), respectively]. IL-6 rs1800796 and HSPD1 rs2605039 had interactions with diabetes on breast cancer risk. Among women with CC genotype of IL-6 rs1800796 or GG genotype of HSPD1 rs2605039, diabetic individuals had a remarkably increased risk of breast cancer compared to non-diabetic women with ORs and 95%CIs of 2.53 (1.45, 4.41) and 6.40 (2.29, 17.87), respectively. GT/TT genotypes of HSPD1 rs2605039 was also associated with a better progression free survival for breast cancer patients [HR (95%CI): 0.70 (0.49, 0.99)]. Our results suggest that the contribution of diabetes to breast cancer risk might be modified by IL-6 rs1800796 and HSPD1 rs2605039. Diabetes and HSPD1 rs2605039 might also influence breast cancer prognosis. [ABSTRACT FROM AUTHOR]